Induction of corticostriatal LTP by 3-nitropropionic acid requires the activation of mGluR1/PKC pathway

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder typically affecting individuals in midlife. HD is characterized by the selective loss of striatal spiny neurons, while large cholinergic interneurons are spared. An impaired mitochondrial complex II (succinate dehydrogenase, SD) activity is known as a prominent metabolic alteration in HD. Accordingly, chronic treatment with 3-nitropropionic acid (3-NP), an irreversible SD inhibitor, mimics motor abnormalities and pathology of HD in several animal models. We have previously shown that in vitro application of 3-NP induces a long-term potentiation (LTP) of corticostriatal synaptic transmission through NMDA glutamate receptor. Since this 3-NP-induced LTP (3-NP-LTP) is shown by striatal spiny neurons, but not by cholinergic interneurons, it might play a role in the regional and cell type-specific neuronal death observed in HD. Here we investigate the role of group I metabotropic glutamate receptors (mGluRs) in the induction of 3-NP-LTP. We report that selectively blocking mGluR1, but not mGluR5, suppresses 3-NP-LTP induction. Moreover, we show that a PKC-mediated mechanism is involved in the formation of 3-NP-LTP. Characterizing the cellular mechanisms underlying 3-NP-LTP may provide new insights to better understand the processes leading to the selective neuronal loss observed in HD.

[1]  Greenamyre Jt,et al.  Bioenergetics and glutamate excitotoxicity. , 1996 .

[2]  P. Conn,et al.  Phosphorylation of Mitogen‐Activated Protein Kinase in Cultured Rat Cortical Glia by Stimulation of Metabotropic Glutamate Receptors , 1998, Journal of neurochemistry.

[3]  P. Greengard,et al.  D(2) dopamine receptors induce mitogen-activated protein kinase and cAMP response element-binding protein phosphorylation in neurons. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[4]  M. Beal,et al.  Chronic 3-Nitropropionic Acid Treatment in Baboons Replicates the Cognitive and Motor Deficits of Huntington’s Disease , 1996, The Journal of Neuroscience.

[5]  J. Geddes,et al.  Calpain Facilitates the Neuron Death Induced by 3‐Nitropropionic Acid and Contributes to the Necrotic Morphology , 2003, Journal of neuropathology and experimental neurology.

[6]  R. Porter,et al.  Inhibition of Succinate Dehydrogenase by Malonic Acid Produces an “Excitotoxic” Lesion in Rat Striatum , 1993, Journal of neurochemistry.

[7]  J. Manzanares,et al.  Alleviation of motor hyperactivity and neurochemical deficits by endocannabinoid uptake inhibition in a rat model of Huntington's disease , 2002, Synapse.

[8]  M E Greenberg,et al.  Calcium signaling in neurons: molecular mechanisms and cellular consequences. , 1995, Science.

[9]  M. Beal,et al.  Mitochondria in Neurodegeneration: Bioenergetic Function in Cell Life and Death , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[10]  A. Ludolph,et al.  3-Nitropropionic Acid - Exogenous Animal Neurotoxin and Possible Human Striatal Toxin , 1991, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[11]  P. Calabresi,et al.  Experimental Parkinsonism Alters Endocannabinoid Degradation: Implications for Striatal Glutamatergic Transmission , 2002, The Journal of Neuroscience.

[12]  J. Cooper,et al.  Mitochondrial defect in Huntington's disease caudate nucleus , 1996, Annals of neurology.

[13]  Joseph B. Martin,et al.  Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid , 1986, Nature.

[14]  Sukhwinder Thandi,et al.  Group‐I metabotropic glutamate receptors, mGlu1a and mGlu5a, couple to extracellular signal‐regulated kinase (ERK) activation via distinct, but overlapping, signalling pathways , 2002, Journal of neurochemistry.

[15]  P. Calabresi,et al.  Post-receptor mechanisms underlying striatal long-term depression , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[16]  P. Calabresi,et al.  Striatal spiny neurons and cholinergic interneurons express differential ionotropic glutamatergic responses and vulnerability: Implications for ischemia and Huntington's disease , 1998, Annals of neurology.

[17]  B. Hyman,et al.  Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  J. Geddes,et al.  Influence of cytosolic and mitochondrial Ca2+, ATP, mitochondrial membrane potential, and calpain activity on the mechanism of neuron death induced by 3-nitropropionic acid , 2003, Neurochemistry International.

[19]  F. Nicoletti,et al.  Group-I metabotropic glutamate receptors: hypotheses to explain their dual role in neurotoxicity and neuroprotection , 1999, Neuropharmacology.

[20]  U. Gerber,et al.  Two Distinct Signaling Pathways Upregulate NMDA Receptor Responses via Two Distinct Metabotropic Glutamate Receptor Subtypes , 2002, The Journal of Neuroscience.

[21]  T. Tamaoki,et al.  Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. , 1989, Biochemical and biophysical research communications.

[22]  P. Calabresi,et al.  The corticostriatal projection: from synaptic plasticity to dysfunctions of the basal ganglia , 1996, Trends in Neurosciences.

[23]  P. Parker,et al.  Isoenzyme specificity of bisindolylmaleimides, selective inhibitors of protein kinase C. , 1993, The Biochemical journal.

[24]  P. Calabresi,et al.  Enhancement of NMDA responses by group I metabotropic glutamate receptor activation in striatal neurones , 1997, British journal of pharmacology.

[25]  G. Gobbel,et al.  Apoptosis in the striatum of rats following intraperitoneal injection of 3-nitropropionic acid , 1997, Brain Research.

[26]  D. Tagle,et al.  Recent advances in understanding the pathogenesis of Huntington's disease , 1999, Trends in Neurosciences.

[27]  P. Calabresi,et al.  Endogenous ACh enhances striatal NMDA‐responses via M1‐like muscarinic receptors and PKC activation , 1998, The European journal of neuroscience.

[28]  G Bernardi,et al.  Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal neurons , 2001, Neuroscience.

[29]  D. Condorelli,et al.  Activation of metabotropic glutamate receptors coupled to inositol phospholipid hydrolysis amplifies NMDA-induced neuronal degeneration in cultured cortical cells , 1995, Neuropharmacology.

[30]  N. Reynolds,et al.  Differential responses of extracellular GABA to intrastriatal perfusions of 3-nitropropionic acid and quinolinic acid in the rat , 1997, Brain Research.

[31]  J. Geddes,et al.  Mechanisms of Cell Death Induced by the Mitochondrial Toxin 3-Nitropropionic Acid: Acute Excitotoxic Necrosis and Delayed Apoptosis , 1997, The Journal of Neuroscience.

[32]  K. Nozaki,et al.  3-Nitropropionic acid induces poly(ADP-ribosyl)ation and apoptosis related gene expression in the striatum in vivo , 1997, Neuroscience Letters.

[33]  M. Berridge.  Neuronal Calcium Signaling , 1998, Neuron.

[34]  E. Meli,et al.  Protection with metabotropic glutamate 1 receptor antagonists in models of ischemic neuronal death: time-course and mechanisms , 1999, Neuropharmacology.

[35]  P. Calabresi,et al.  The neostriatum beyond the motor function: experimental and clinical evidence. , 1997, Neuroscience.

[36]  A. Tobin,et al.  Metabolic Compromise with Systemic 3-Nitropropionic Acid Produces Striatal Apoptosis in Sprague–Dawley Rats but Not in BALB/c ByJ Mice , 1998, Experimental Neurology.

[37]  R. Gross,et al.  3-Nitropropionic acid exacerbates N-methyl-d-aspartate toxicity in striatal culture by multiple mechanisms , 1998, Neuroscience.

[38]  A. Cooper,et al.  The selective vulnerability of striatopallidal neurons , 1999, Progress in Neurobiology.

[39]  J. Pin,et al.  The metabotropic glutamate receptors: structure, activation mechanism and pharmacology. , 2002, Current drug targets. CNS and neurological disorders.

[40]  P. Greengard,et al.  Inhibition of Mitochondrial Complex II Induces a Long-Term Potentiation of NMDA-Mediated Synaptic Excitation in the Striatum Requiring Endogenous Dopamine , 2001, The Journal of Neuroscience.

[41]  S. Avraham,et al.  Glutamate‐Stimulated Activation of DNA Synthesis via Mitogen‐Activated Protein Kinase in Primary Astrocytes , 2000, Journal of neurochemistry.

[42]  R. Duvoisin,et al.  The metabotropic glutamate receptors: Structure and functions , 1995, Neuropharmacology.

[43]  M. Beal,et al.  Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia , 1997, Annals of neurology.

[44]  Charles J. Wilson,et al.  Membrane potential synchrony of simultaneously recorded striatal spiny neurons in vivo , 1998, Nature.

[45]  C. Epstein,et al.  3‐Nitropropionic Acid Neurotoxicity Is Attenuated in Copper/Zinc Superoxide Dismutase Transgenic Mice , 1995, Journal of neurochemistry.

[46]  P. Conn,et al.  Metabotropic glutamate receptors in brain function and pathology. , 1993, Trends in pharmacological sciences.

[47]  C. Tanaka,et al.  The loss of βII-protein kinase C in the striatum from patients with Huntington's disease , 1992, Brain Research.

[48]  M. Beal,et al.  Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[49]  A. Morton,et al.  Dopamine Modulates the Susceptibility of Striatal Neurons to 3-Nitropropionic Acid in the Rat Model of Huntington’s Disease , 1998, The Journal of Neuroscience.

[50]  J. Penney,et al.  Metabotropic receptors in excitotoxicity: (S)-4-carboxy-3-hydroxyphenylglycine ((S)-4C3HPG) protects against rat striatal quinolinic acid lesions , 1995, Neuroscience Letters.

[51]  G Bernardi,et al.  Synaptic transmission in the striatum: from plasticity to neurodegeneration , 2000, Progress in Neurobiology.

[52]  G. Gobbel,et al.  Decreased expression of bcl-2 and bcl-x mRNA coincides with apoptosis following intracerebral administration of 3-nitropropionic acid , 1998, Brain Research.

[53]  E. Meli,et al.  Metabotropic glutamate 1 (mGlu1) receptor antagonists enhance GABAergic neurotransmission: a mechanism for the attenuation of post-ischemic injury and epileptiform activity? , 2002, Neuropharmacology.

[54]  R. Gereau,et al.  Metabotropic Glutamate Receptor Subtypes 1 and 5 Are Activators of Extracellular Signal-Regulated Kinase Signaling Required for Inflammatory Pain in Mice , 2001, The Journal of Neuroscience.

[55]  S. Nakanishi,et al.  Activation of the extracellular signal‐regulated kinase 2 by metabotropic glutamate receptors , 1999, The European journal of neuroscience.

[56]  G. Perrault,et al.  Further evidence for differences between non-selective and BZ-1 (ω1) Selective, benzodiazepine receptor ligands in murine models of “state” and “trait” Anxiety , 1996, Neuropharmacology.

[57]  G Bernardi,et al.  Activation of metabotropic glutamate receptor subtype 1/protein kinase C/mitogen-activated protein kinase pathway is required for postischemic long-term potentiation in the striatum. , 2001, Molecular pharmacology.

[58]  G. Gobbel,et al.  Journal of Cerebral Blood Flow and Metabolism Excitotoxicity Is Required for Induction of Oxidative Stress and Apoptosis in Mouse Striatum by the Mitochondrial Toxin, 3-nitropropionic Acid , 2022 .

[59]  J. B. Martin,et al.  Selective sparing of a class of striatal neurons in Huntington's disease. , 1985, Science.

[60]  P. Calabresi,et al.  Corticostriatal LTP requires combined mGluR1 and mGluR5 activation , 2003, Neuropharmacology.

[61]  P. Calabresi,et al.  Selective Blockade of Type-1 Metabotropic Glutamate Receptors Induces Neuroprotection by Enhancing Gabaergic Transmission , 2001, Molecular and Cellular Neuroscience.

[62]  D L Price,et al.  Genetic neurodegenerative diseases: the human illness and transgenic models. , 1998, Science.

[63]  A. Makriyannis,et al.  Compounds acting at the endocannabinoid and/or endovanilloid systems reduce hyperkinesia in a rat model of Huntington's disease , 2003, Journal of neurochemistry.

[64]  J. Pin,et al.  Pharmacology and functions of metabotropic glutamate receptors. , 1997, Annual review of pharmacology and toxicology.

[65]  D. Choi,et al.  The inhibitory mGluR agonist, s-4-carboxy-3-hydroxy-phenylglycine selectively attenuates NMDA neurotoxicity and oxygen-glucose deprivation-induced neuronal death , 1995, Neuropharmacology.

[66]  P. Calabresi,et al.  Long‐term Potentiation in the Striatum is Unmasked by Removing the Voltage‐dependent Magnesium Block of NMDA Receptor Channels , 1992, The European journal of neuroscience.

[67]  J. Penney,et al.  3‐Nitropropionic Acid Toxicity in the Striatum , 1994, Journal of neurochemistry.

[68]  W. Maragos,et al.  Neuronal cell death in Huntington’s disease: a potential role for dopamine , 2000, Trends in Neurosciences.

[69]  D. Butterfield,et al.  3-Nitropropionic acid induced in vivo protein oxidation in striatal and cortical synaptosomes: insights into Huntington's disease , 2000, Brain Research.

[70]  P. Greengard,et al.  Dopamine and cAMP-Regulated Phosphoprotein 32 kDa Controls Both Striatal Long-Term Depression and Long-Term Potentiation, Opposing Forms of Synaptic Plasticity , 2000, The Journal of Neuroscience.

[71]  H. Hidaka,et al.  Pharmacology of protein kinase inhibitors. , 1992, Annual review of pharmacology and toxicology.

[72]  M. Erecińska,et al.  Effects of 3‐Nitropropionic Acid on Synaptosomal Energy and Transmitter Metabolism: Relevance to Neurodegenerative Brain Diseases , 1994, Journal of neurochemistry.

[73]  F. Nicoletti,et al.  Neuroprotective activity of the potent and selective mGlu1a metabotropic glutamate receptor antagonist, (+)-2-methyl-4 carboxyphenylglycine (LY367385): comparison with LY357366, a broader spectrum antagonist with equal affinity for mGlu1a and mGlu5 receptors , 1999, Neuropharmacology.

[74]  B. Meldrum,et al.  Glutamate as a neurotransmitter in the brain: review of physiology and pathology. , 2000, The Journal of nutrition.

[75]  M. Behrens,et al.  Antagonists for group I mGluRs attenuate excitotoxic neuronal death in cortical cultures , 1998, The European journal of neuroscience.

[76]  M. Greenberg,et al.  Calcium Influx via the NMDA Receptor Induces Immediate Early Gene Transcription by a MAP Kinase/ERK-Dependent Mechanism , 1996, The Journal of Neuroscience.